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Article

Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons

1
Instituto de Investigaciones Bioquímicas de Bahía Blanca, Bahía Blanca 8000, Argentina
2
Laboratory of Molecular Neurobiology, Institute for Biomedical Research, UCA–CONICET, Faculty of Medical Sciences, Catholic University of Argentina, Av. Alicia Moreau de Justo, Buenos Aires 1600 C1107AAZ, Argentina
*
Author to whom correspondence should be addressed.
Current address: Instituto de Tecnología en Polímeros y Nanotecnología (ITPN-UBA-CONICET), Facultad de Arquitectura, Diseño y Urbanismo, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires 1428, Argentina.
Academic Editors: Luís M. S. Loura, Maria João Moreno and Anass Jawhari
Molecules 2020, 25(20), 4838; https://doi.org/10.3390/molecules25204838
Received: 14 September 2020 / Revised: 15 October 2020 / Accepted: 18 October 2020 / Published: 20 October 2020
(This article belongs to the Special Issue Membrane Structure and Function)
Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cells were evaluated in the 0.01–1 µM range. Chronic (14 days) lovastatin treatment augmented cell-surface levels of α7 and α4 nAChRs, as measured by fluorescence microscopy and radioactive ligand binding assays. This was accompanied in both cases by an increase in total protein receptor levels as determined by Western blots. At low lovastatin concentrations (10–100 nM), the increase in α4 nAChR in neurites was higher than in neuronal cell somata; the opposite occurred at higher (0.5–1 µM) lovastatin concentrations. In contrast, neurite α7 nAChRs raised more than somatic α7 nAChRs at all lovastatin concentrations tested. These results indicate that cholesterol levels homeostatically regulate α7 and α4 nAChR levels in a differential manner through mechanisms that depend on statin concentration and receptor localization. The neuroprotective pleomorphic effects of statins may act by reestablishing the homeostatic equilibrium. View Full-Text
Keywords: nicotinic acetylcholine receptor; cholesterol; hippocampal neurons; upregulation; homeostatic regulation; Alzheimer disease nicotinic acetylcholine receptor; cholesterol; hippocampal neurons; upregulation; homeostatic regulation; Alzheimer disease
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MDPI and ACS Style

Borroni, V.; Kamerbeek, C.; Pediconi, M.F.; Barrantes, F.J. Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons. Molecules 2020, 25, 4838. https://doi.org/10.3390/molecules25204838

AMA Style

Borroni V, Kamerbeek C, Pediconi MF, Barrantes FJ. Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons. Molecules. 2020; 25(20):4838. https://doi.org/10.3390/molecules25204838

Chicago/Turabian Style

Borroni, Virginia, Constanza Kamerbeek, María F. Pediconi, and Francisco J. Barrantes. 2020. "Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons" Molecules 25, no. 20: 4838. https://doi.org/10.3390/molecules25204838

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